Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphorylation.

Abstract

Iron deficiency impairs skeletal muscle metabolism. The underlying mechanisms are incompletely characterised, but animal and human experiments suggest the involvement of signalling pathways co-dependent upon oxygen and iron availability, including the pathway associated with hypoxia-inducible factor (HIF). We performed a prospective, case-control, clinical physiology study to explore the effects of iron deficiency on human metabolism, using exercise as a stressor. Thirteen iron-deficient (ID) individuals and thirteen iron-replete (IR) control participants each underwent 31P-magnetic resonance spectroscopy of exercising calf muscle to investigate differences in oxidative phosphorylation, followed by whole-body cardiopulmonary exercise testing. Thereafter, individuals were given an intravenous (IV) infusion, randomised to either iron or saline, and the assessments repeated ~ 1 week later. Neither baseline iron status nor IV iron significantly influenced high-energy phosphate metabolism. During submaximal cardiopulmonary exercise, the rate of decline in blood lactate concentration was diminished in the ID group (P = 0.005). Intravenous iron corrected this abnormality. Furthermore, IV iron increased lactate threshold during maximal cardiopulmonary exercise by ~ 10%, regardless of baseline iron status. These findings demonstrate abnormal whole-body energy metabolism in iron-deficient but otherwise healthy humans. Iron deficiency promotes a more glycolytic phenotype without having a detectable effect on mitochondrial bioenergetics.

• Authors: Matthew C Frise, David A Holdsworth, Andrew W Johnson, Yu Jin Chung, M Kate Curtis, Pete J Cox, Kieran Clarke, Damian J Tyler, David J Roberts, Peter J Ratcliffe, Keith L Dorrington, Peter A Robbins
• Journal: Scientific reports (Sci Rep) Vol. 12 Issue 1 Pg. 998 (01 19 2022) ISSN: 2045-2322 [Electronic] England
• PMID: 35046429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Lactic Acid
• Iron

Topics

• Administration, Intravenous
• Adult
• Case-Control Studies
• Energy Metabolism (physiology)
• Exercise (physiology)
• Female
• Humans
• Iron (administration & dosage)
• Iron Deficiencies (metabolism)
• Lactic Acid (blood)
• Male
• Muscle, Skeletal (metabolism)
• Oxidative Phosphorylation
• Prospective Studies